2019年6月4日，欧洲肿瘤内科学会《肿瘤学报》在线发表葡萄牙尚帕利莫基金会临床中心、欧洲乳腺癌联盟塞浦路斯分部、日本东京癌症研究会有明医院、法国奥弗涅大学让佩林中心、巴黎文理研究大学居里研究所、西班牙纳瓦拉大学马德里医院、瑞典隆德大学马尔默分校、波兰格但斯克医科大学起草的欧洲肿瘤内科学会临床实践指南：早期乳腺癌的诊断、治疗和随访，对2015年发表的欧洲肿瘤内科学会原发乳腺癌诊断、治疗和随访临床实践指南第9版进行了更新。草案全文共77页，其中正文39页、参考文献21页、图表17页。以下为欧洲肿瘤内科学会临床实践指南：早期乳腺癌的治疗推荐意见。
治疗组织机构推荐意见：
应该在乳腺专科或中心进行治疗，由乳腺癌专业多学科团队提供，至少包括肿瘤内科医师、乳腺外科医师、肿瘤放疗科医师、乳腺放射科医师、乳腺病理科医师、乳腺专科护士（或经过类似专业培训的医疗执业者）【III级证据A级推荐】。
如有指征，乳腺专科或中心应该拥有或能够将患者转诊给整形或重建外科医师、心理科医师、物理治疗师、遗传咨询师【III级证据A级推荐】。
应该由乳腺专科护士或经过类似专业培训的医疗执业者担任患者导医【III级证据A级推荐】。
Organisation of care Recommendations:
Treatment should be carried out in specialised breast units/centres and provided by a multidisciplinary team specialised in breast cancer, consisting of at least medical oncologists, breast surgeons, radiation oncologists, breast radiologists, breast pathologists and breast nurses (or similarly trained and specialised healthcare practitioners) [III, A].
The breast unit/centre should have or be able to refer patients to plastic/reconstructive surgeons, psychologists, physiotherapists and geneticists when appropriate [III, A].
A breast nurse or a similarly trained and specialised healthcare practitioner should be available to act as a patient navigator [III, B].
患者知情和参与决策推荐意见：
应该以全面并且易于理解的形式，反复（同时以口头和书面形式）提供关于诊断和治疗选择的信息【V级证据A级推荐】。
建议使用可靠的，以患者为中心的网站或类似的信息来源【V级证据A级推荐】。
应该让患者积极参与所有治疗决策【V级证据A级推荐】。
治疗策略的选择，应该根据患者的肿瘤负荷（原发肿瘤的大小和部位、病灶数量、淋巴结影响程度）和生物学（病理学，包括生物标志和基因表达）以及年龄、绝经状况、一般健康状况、偏好【V级证据A级推荐】。
应该将年龄与其他因素一起考虑，不应成为取消或推荐某一治疗的唯一决定因素【V级证据A级推荐】。
对于年轻的绝经前患者，开始任何全身治疗之前，应该讨论生育问题以及患者需要时的生育能力保留技术【V级证据A级推荐】。
图1、早期乳腺癌治疗流程
Patient information and involvement in decision-making Recommendations:
Information on diagnosis and treatment choice should be given repeatedly (both verbally and in writing) in a comprehensive and easily understandable form [V, A].
The use of reliable, patient-centred websites or similar sources of information is recommended [V, A].
Patients should be actively involved in all management decisions [V, A].
The choice of treatment strategy should be based on the tumour burden/location (size and location of primary tumour, number of lesions, extent of lymph node involvement) and biology (pathology, including biomarkers and gene expression), as well as the age, menopausal status, general health status and preferences of the patient [V, A].
Age should be taken into consideration in conjunction with other factors and should not be the sole determinant for withholding or recommending a treatment [V, A].
In younger premenopausal patients, fertility issues and, when desired by the patient, fertility-preservation techniques should be discussed, before the initiation of any systemic treatment [V, A].
乳房保留手术（保乳手术）推荐意见：
对于大多数早期乳腺癌患者，保乳手术是首选的局部治疗选择，当有必要时，对于常规技术具有挑战的病例，通过肿瘤整形技术，可以保持良好的美学效果【I级证据A级推荐】。
对切缘进行仔细的组织学检查至关重要，必需保证切缘无肿瘤，对于原位病变，切缘首选大于2毫米【I级证据A级推荐】。
Breast-conserving surgery Recommendations:
BCS is the preferred local treatment option for the majority of early breast cancer patients, with the use of oncoplastic techniques, to maintain good cosmetic outcomes in technically challenging cases, when needed [I, A].
Careful histological assessment of resection margins is essential. No tumour at the inked margin is required and > 2 mm for in situ disease is preferred [I, A].
乳房切除手术推荐意见：
应该为所有需要乳房切除手术的女性提供乳房重建【V级证据A级推荐】。
除了炎性乳腺癌，绝大多数患者应该即刻乳房重建【V级证据A级推荐】。
应该考虑解剖学因素、治疗因素、患者因素和偏好，为每位患者单独讨论最佳重建技术【V级证据A级推荐】。
Mastectomy Recommendations:
Breast reconstruction should be available and proposed to all women requiring mastectomy [V, A].
Immediate breast reconstruction should be offered to the vast majority of patients, except for those presenting with inflammatory cancer [V, A].
The optimal reconstruction technique for each patient should be discussed individually taking into account anatomic, treatment- and patient-related factors and preferences [V, A].
腋窝管理推荐意见：
前哨淋巴结活检（而非全部淋巴结清除）是早期临床淋巴结阴性乳腺癌腋窝分期的处理标准【II级证据A级推荐】。
对于虽然前哨淋巴结活检阳性，但是腋窝病变负荷较低（微转移或一到两个前哨淋巴结转移）患者，不需要进一步腋窝手术，推荐术后乳房切向放疗【II级证据A级推荐】。
无论乳房手术类型如何，腋窝放疗都是前哨淋巴结活检阳性患者的合理选择【II级证据A级推荐】。
Advances in axillary management Recommendations:
SLNB, rather than full nodal clearance, is the standard of care for axillary staging in early, clinically node-negative breast cancer [II, A].
Further axillary surgery following positive SLNB is not required in case of low axillary disease burden (micrometastases or one to two SLNs containing metastases), treated with postoperative tangential breast RT [II, A].
Axillary radiation is a valid alternative in patients with positive SLNB, irrespective of the type of breast surgery [II, A].
原位恶性肿瘤（上皮内瘤变）手术推荐意见：
保乳术后，对于乳腺导管原位癌，无论全乳放疗，或者全乳切除，均为可以接受的治疗选择【I级证据A级推荐】。
当用保乳手术治疗时，对于全乳放疗的乳腺导管原位癌，切缘2毫米足够【II级证据A级推荐】。
除了肿瘤较大和（或）分级较高的患者，对于乳腺导管原位癌，不应该常规进行前哨淋巴结活检，尤其对于需要乳房切除手术的患者【II级证据A级推荐】。
Surgery for in situ malignancy (intraepithelial neoplasia) Recommendations:
BCS followed by WBRT or total mastectomy are acceptable treatment options for DCIS [I, A].
When treated with BCS, a 2 mm margin is adequate in DCIS treated with WBRT [II, B].
SLNB should not be routinely carried out in DCIS, apart from patients with large and/or high-grade tumours, especially when mastectomy is required [V, D].
隐匿型乳腺癌治疗推荐意见：
隐匿型乳腺癌首选局部治疗为腋窝淋巴结清扫和全乳放疗【IV级证据B级推荐】。
Management of occult breast cancer Recommendations:
The preferred locoregional management of occult breast cancer is ALND and WBRT [IV, B].
减少风险（预防性）乳房切除手术推荐意见：
可以向风险极高（例如携带BRCA基因突变或有淋巴瘤胸部放疗史）女性提供减少风险手术（预防性双侧乳房切除手术和重建）。此类手术之前，必须进行仔细的基因评定和心理咨询，并且还应该商讨密切监测的选择【III级证据A级推荐】。
对于首选双侧乳房切除手术（包括对侧减少风险手术）而非首选保乳手术的低风险患者，应该告知对于早期乳腺癌患者，保乳手术治疗与乳房切除手术相比，生存结局并不差，甚至更好【V级证据A级推荐】。
Risk-reducing mastectomy Recommendations:
Risk-reducing surgery (with prophylactic bilateral mastectomy and reconstruction) may be offered to women at very high risk, such as BRCA1 or BRCA2 mutation carriers or those who have had previous chest RT for lymphoma. Careful genetic assessment and psychological counselling are mandatory before undertaking such surgery, and the option of intense surveillance should also be discussed [III, A].
Non-high-risk patients who opt for bilateral mastectomy (incorporating contralateral risk-reducing surgery) rather than the preferred breast conservation should be counselled that survival outcomes in patients with early-stage breast cancer treated with BCS might be even better (and certainly not worse) than those treated with mastectomy [V, A].
初步全身治疗后的手术推荐意见：
初步全身治疗后的手术，应该按照早期乳腺癌的常规进行，并且考虑治疗前肿瘤特征以及治疗后结局【II级证据A级推荐】。
如果考虑保乳手术，必须进行肿瘤部位标记【V级证据A级推荐】，并且手术前后应该进行磁共振检查【II级证据A级推荐】。
对于临床阴性腋窝，虽然前哨淋巴结活检可于初步全身治疗之前或之后进行，但是首选初步全身治疗后前哨淋巴结活检【II级证据A级推荐】。
对于手术前腋窝转移转为阴性的患者，可对筛选后病例进行前哨淋巴结活检，如果为阴性，可避免进一步腋窝手术【II级证据A级推荐】。
初步全身治疗后，前哨淋巴结活检发现任何肿瘤残留，提示进行腋窝淋巴结清扫【II级证据A级推荐】。
Surgery after primary systemic therapy Recommendations:
Surgery following PST should be carried out according to general rules for early breast cancer and considering the baseline tumour characteristics as well as the post-treatment outcomes [II, A].
If BCS is anticipated, marking of the tumour site must be carried out [V, A] and pre-and post-treatment breast MRI should be performed [II, A].
In clinically-negative axilla, although SLNB may be carried out either pre- or post-PST, post-PST SLNB is preferred [II, A].
In patients with baseline axillary involvement converting to negative, SLNB may be carried out in selected cases, and, if negative, further axillary surgery may be avoided [II, B].
Identification of any tumour deposits in post-PST SLNB prompts ALND [II, B].
保乳术后的全乳放疗推荐意见：
强烈推荐保乳术后进行术后放疗【I级证据A级推荐】。
推荐追加局部放疗，以减少局部复发风险较高患者的乳房复发风险【I级证据A级推荐】。
Whole-breast radiotherapy after breast-conserving surgery Recommendations:
Postoperative RT is strongly recommended after BCS [I, A].
Boost RT is recommended to reduce the risk of in-breast relapse in patients at higher risk of local recurrence [I, A].
保乳术后追加部分乳房放疗推荐意见：
对于局部复发风险较低的患者，追加部分乳房放疗为可以接受的治疗选择之一【III级证据C级推荐】。
Accelerated partial-breast radiotherapy after breast-conserving surgery Recommendations:
·APBI is an acceptable treatment option in patients with a low risk for local recurrence [III, C].
乳房切除术后放疗推荐意见：
乳房切除术后放疗推荐用于高风险患者，包括有切缘阳性、腋窝淋巴结阳性、T3～T4期肿瘤患者【I级证据A级推荐】；对于1～3个腋窝淋巴结阳性的患者也应该考虑【I级证据A级推荐】。
Post-mastectomy radiotherapy Recommendations:
PMRT is recommended for high-risk patients, including those with involved resection margins, involved axillary lymph nodes and T3-T4 tumours [I, A]; it should also be considered in patients with 1-3 positive axillary lymph nodes [I, A].
淋巴引流区域放疗推荐意见：
对于淋巴结阳性患者，建议对胸壁和全部淋巴结进行扩大放疗（特定区域淋巴结放疗的作用尚不明确）【I级证据B级推荐】。
腋窝淋巴结清扫后，不应该对腋窝手术部位进行常规腋窝放疗【I级证据E级推荐】。
Regional radiotherapy Recommendations:
Comprehensive nodal RT is recommended for patients with involved lymph nodes (the role of irradiating particular nodal volumes is poorly defined; see details in text) [I, B].
After ALND, routine axillary irradiation should not be done to the operated part of the axilla [I, E].
放疗和乳房重建推荐意见：
如有指征，可在即刻乳房重建后进行术后放疗【III级证据A级推荐】。
有必要加强多学科和互动式患者参与，对乳房重建和放疗的顺序和类型最佳组合进行个体化【V级证据A级推荐】。
Radiotherapy and breast reconstruction Recommendations:
Postoperative RT, if indicated, can be administered after immediate breast reconstruction [III, A].
An intensive multidisciplinary and interactive patient-involving approach is required to individualise the best combination of the sequence and type of breast reconstruction and RT [V, A].
放疗剂量分割推荐意见：
对于乳腺癌的常规术后放疗，推荐大分割疗程（分割为15～16次，每次≤3Gy）【I级证据A级推荐】。
Radiotherapy doses and fractionation Recommendations:
Moderate hypofractionation schedules (15-16 fractions of ≤ 3 Gy/fraction) are recommended for routine postoperative RT of breast cancer [I, A].
原位恶性肿瘤（上皮内瘤变）放疗推荐意见：
对于大多数接受保乳手术治疗的乳腺导管原位癌女性，推荐全乳放疗【I级证据A级推荐】。
对于低风险乳腺导管原位癌患者，可以选择免去放疗【V级证据B级推荐】。
对于局部复发风险较高的患者，可考虑瘤床追加放疗【III级证据A级推荐】。
对于乳腺导管原位癌乳房切除术后患者，不推荐放疗【I级证据E级推荐】。
Radiotherapy for in situ malignancy (intraepithelial neoplasia) Recommendations:
·WBRT is recommended for the majority of women with DCIS treated with BCS [I, A].
·In patients with low-risk DCIS, omitting radiation is an option [V, B].
·Tumour bed boost can be considered for patients at higher risk for local failure [III, B].
·PMRT is not recommended for DCIS [I, E].
术前新辅助或术后辅助全身治疗推荐意见：
术后辅助全身治疗推荐术后3～6周内开始【I级证据A级推荐】，术前新辅助全身治疗推荐诊断和分期完成后尽快开始（理想情况2～4周内）【V级证据A级推荐】。
术后辅助全身治疗的决策应该根据个体复发风险（取决于肿瘤负荷和肿瘤生物学特征）、对特定治疗类型敏感性的预测、获益及其相关的短期和长期毒性、患者的生物学年龄、一般健康状况、合并症和偏好【V级证据A级推荐】。
所有管腔型乳腺癌都应该进行内分泌治疗【I级证据A级推荐】。
大多数管腔A型乳腺癌不需要化疗，除非病变负荷高【I级证据A级推荐】。
对于管腔B型HER2阴性患者，是否化疗取决于个体复发风险、内分泌治疗效果推测、患者偏好【V级证据A级推荐】。
对于术后辅助化疗指征不确定的病例（考虑所有临床和病理因素后），可以进行尿激酶型纤溶酶原激活物（uPA）纤溶酶原激活物抑制蛋白1（PAI1）表达分析【I级证据A级推荐】或多基因表达分析，例如70基因Mamma Print【I级证据A级推荐】、21基因Oncotype DX【I级证据A级推荐】、50基因Prosigna、8基因Endo predict、乳腺癌指数。
管腔B型HER2阳性乳腺癌应该进行化疗＋内分泌治疗＋抗HER2治疗【I级证据A级推荐】。对于筛选后低风险患者（T1abN0）可以进行抗HER2治疗和内分泌治疗而不化疗【III级证据A级推荐】。
三阴性乳腺癌患者应该进行化疗，可能除了风险较低的特殊组织学亚型，例如分泌性或腺样囊性乳腺癌或极早期（T1aN0）乳腺癌【I级证据A级推荐】。
HER2阳性乳腺癌应该进行化疗＋抗HER2治疗，可能除了风险极低的病例，例如极早期（T1aN0）乳腺癌【I级证据A级推荐】。
化疗不应该与内分泌治疗同时进行【II级证据D级推荐】，除了用于保护卵巢功能的促性腺激素释放激素类似物【I级证据A级推荐】
抗HER2治疗可以常规联合非蒽环类化疗、内分泌治疗和放疗【I级证据A级推荐】。
·抗HER2治疗、内分泌治疗、非蒽环类、非紫杉类化疗期间可以安全地进行放疗【III级证据A级推荐】。
·如果进行化疗和放疗，化疗通常应该早于放疗【V级证据A级推荐】。
图2、根据标志表达和分子学表面型进行新辅助、辅助全身治疗选择
(Neo)Adjuvant systemic treatment Recommendations:
Adjuvant systemic treatment should preferably start within 3-6 weeks after surgery [I, A] and neoadjuvant systemic therapy should start as soon as diagnosis and staging is completed (ideally within 2-4 weeks) [V, A].
The decision on adjuvant systemic therapies should be based on an individual's risk of relapse (which depends on tumour burden and tumour biology), the predicted sensitivity to particular types of treatment, the benefit from their use and their associated short- and long-term toxicities, the patient's biological age, general health status, comorbidities and preferences [V, A].
All luminal-like cancers should be treated with ET [I, A].
Most luminal A-like tumours do not require ChT, except those with high disease burden [I, A].
ChT use in luminal B-like HER2-negative patients depends on individual risk of recurrence, presumed responsiveness to ET and patient preferences [V, A].
In cases of uncertainty regarding indications for adjuvant ChT (after consideration of all clinical and pathological factors), expression of uPA-PAI1 [I, A] or gene expression assays, such as MammaPrint, Oncotype DX, Prosigna, Endopredict or Breast Cancer Index, can be used [I, A for the first two tests].
Luminal B-like HER2-positive tumours should be treated with ChT, ET and anti-HER2 therapy [I, A]. In selected low-risk patients (T1abN0), the combination of anti-HER2 therapy and ET alone may be used [III, B].
Patients with TNBC should receive ChT, with the possible exception of low-risk 'special histological subtypes' such as secretory or adenoid cystic carcinomas or very early (T1aN0) tumours [I, A].
HER2-positive cancers should be treated with ChT plus anti-HER2 therapy, with the possible exception of selected cases with very low risk, such as T1aN0 tumours [I, A].
ChT should not be used concomitantly with ET [II, D], with the exception of gonadotropin-releasing hormone (GnRH) analogues used for ovarian protection [I, A].
Anti-HER2 therapy may routinely be combined with non-anthracycline-based ChT, ET and RT [I, A].
RT may be delivered safely during anti-HER2 therapy, ET and non-anthracycline, non-taxane-based ChT [III, B].
If ChT and RT are to be used, ChT should usually precede RT [V, A].
绝经前患者内分泌治疗推荐意见：
对于绝经前女性，他莫昔芬治疗5～10年为标准方案【I级证据A级推荐】。
对于他莫昔芬治疗前5年期间绝经患者，应该考虑改用来曲唑，取决于远期复发风险预测【II级证据A级推荐】。
对于需要化疗而月经恢复的患者（尤其第1年，至多前2年内），应该强烈考虑内分泌治疗加入卵巢功能抑制【I级证据A级推荐】。
对于高风险患者，可以考虑用芳香酶抑制剂替换他莫昔芬，并且需要有效的卵巢功能抑制、对雌激素水平进行定期生化控制【I级证据A级推荐】。
卵巢功能抑制对于年龄35岁以下不需化疗患者的作用尚不明确，但是年轻的管腔型早期乳腺癌患者结局较差，提示应该进行最有效的内分泌治疗（即与卵巢功能抑制联合）【III级证据A级推荐】。
化疗期间卵巢功能抑制对卵巢功能具有一定保护作用，对肿瘤学结局无不良影响，应该向患者提议【I级证据A级推荐】。不过，对于希望生育的病例，不应该作为唯一的生育能力保留方法【I级证据A级推荐】。
Premenopausal patients Recommendations:
For premenopausal women, tamoxifen for 5-10 years is a standard of care [I, A].
In patients becoming postmenopausal during the first 5 years of tamoxifen, a switch to letrozole should be considered, depending on predicted risk of late recurrence [II, A].
In patients requiring ChT and who recover menses (in particular in the first year but acceptable within the first 2 years), addition of OFS to ET should be strongly considered [I, A].
The role of replacing tamoxifen with an AI can be considered in high-risk patients; if used, it mandates effective OFS, with regular biochemical control of oestrogen levels [I, A].
The role of OFS in patients < 35 years not requiring ChT is not clear, but inferior outcomes of young luminal early breast cancer patients suggest the use of the most effective ET (i.e. combination with OFS) [III, A].
OFS during ChT provides some protection of ovarian function and has no negative impact on oncological outcomes; thus, it should be proposed to patients [I, A]. It should not however be the sole fertility preservation method used, in case of desired pregnancy [I, A].
绝经后患者内分泌治疗推荐意见：
对于绝经后女性，芳香酶抑制剂（非甾体类和甾体类）和他莫昔芬治疗为标准方案【I级证据A级推荐】。
非甾体芳香酶抑制剂和依西美坦可以在他莫昔芬治疗前用，或他莫昔芬治疗2～3年后用，来曲唑和阿那曲唑可以在他莫昔芬治疗5年后作为延长辅助治疗【I级证据A级推荐】。
应该与所有患者讨论延长辅助治疗，除了复发风险极低的患者【I级证据A级推荐】，但是内分泌辅助治疗的最佳持续时间和方案目前尚不明确。芳香酶抑制剂治疗时间超过5年的获益极少【I级证据C级推荐】。
应该建议进行卵巢功能抑制和服用芳香酶抑制剂的患者摄入足够的钙和维生素D3，并且定期进行双能X线吸收（DEXA）扫描评定骨密度【I级证据A级推荐】。
由于CYP2D6多态性作为他莫昔芬辅助治疗决策工具的研究尚未证实，故不推荐【I级证据E级推荐】。
Postmenopausal patients Recommendations:
For postmenopausal women, AIs (both non-steroidal and steroidal) and tamoxifen are considered standard treatments [I, A].
AIs can be used upfront (non-steroidal AI and exemestane), after 2-3 years of tamoxifen (non-steroidal AI and exemestane) or as extended adjuvant therapy, after 5 years of tamoxifen (letrozole and anastrozole) [I, A].
Extended adjuvant therapy should be discussed with all patients, except those with a very low risk of relapse [I, A], but the optimal duration and regimen of adjuvant ET is currently unknown. There is only a minimal benefit for the use of AIs for more than 5 years [I, C].
Patients undergoing OFS and those taking AIs should be advised to have adequate calcium and vitamin D3 intake and undergo periodic assessment of bone mineral density [by dual energy X-ray absorption (DEXA) scan] [I, A].
The study of CYP2D6 polymorphisms as a decision aid regarding the use of adjuvant tamoxifen is not proven and should not be done [I, E].
化疗推荐意见：
化疗应该进行12～24周（4～8轮）【I级证据A级推荐】。
对于大多数患者，蒽环类和紫杉类的先后方案为标准方案【I级证据A级推荐】。
对于筛选后低风险患者，可以考虑4轮蒽环类或紫杉类化疗或环磷酰胺＋甲氨蝶呤＋氟尿嘧啶【II级证据B级推荐】。
非蒽环类方案可以用于有心脏并发症风险的患者【I级证据A级推荐】。
蒽环类方案不应该包括氟尿嘧啶（表柔比星＋环磷酰胺或多柔比星＋环磷酰胺为标准）【I级证据A级推荐】。
铂类化合物不应该常规用于术后辅助化疗【V级证据E级推荐】。
剂量密集方案＋粒细胞集落刺激因子（G-CSF）应该考虑用于高度增殖乳腺癌【I级证据A级推荐】。
Chemotherapy Recommendations:
ChT should be administered for 12-24 weeks (four to eight cycles) [I, A].
Sequential anthracycline/taxane-based regimen is the standard for the majority of patients [I, A].
In selected lower risk patients four cycles of anthracycline- or taxane-based ChT or CMF may be used [II, B].
Non-anthracycline regimens may be used in patients at risk of cardiac complications [I, A].
Anthracycline-based regimens should not include 5-FU (EC or AC is standard) [I, A].
Platinum compounds should not be used routinely in the adjuvant setting [V, E].
The use of dose-dense schedules [with granulocyte colony-stimulating factor (G-CSF) support] should be considered, particularly in highly proliferative tumours [I, A] [158, 159].
抗HER2治疗推荐意见：
曲妥珠单抗术前新辅助或术后辅助治疗非常有效，应该给予所有无禁忌症的HER2阳性早期乳腺癌患者，可能除了筛选后风险极低患者，例如T1aN0乳腺癌【I级证据A级推荐】
如果HER2检测结果最终模棱两可，即使替代方法检测后，也可考虑HER2靶向治疗【V级证据B级推荐】。
曲妥珠单抗术前新辅助或术后辅助治疗一年仍为绝大多数HER2阳性乳腺癌患者的标准方案【I级证据A级推荐】。
对于接受蒽环类、紫杉类化疗的高度筛选后低风险患者，可以讨论曲妥珠单抗持续时间缩短至6个月【I级证据A级推荐】。
曲妥珠单抗通常不应该与蒽环类化疗同时进行【I级证据D级推荐】，可以安全地与非蒽环类化疗（即紫杉类）联合，并且同时比先后更有效【I级证据A级推荐】。
曲妥珠单抗治疗开始前和治疗期间必须定期进行心脏监测【I级证据A级推荐】。
曲妥珠单抗＋拉帕替尼的双重阻断并未带来长期结局改善，故不推荐【I级证据E级推荐】。
术前或术后1年内，高风险（淋巴结阳性或雌激素受体阴性）患者可以考虑曲妥珠单抗＋帕妥珠单抗进行双重阻断【I级证据E级推荐，临床获益量表评分：B】。
对于术前新辅助化疗联合抗HER2治疗完成后残留浸润病变患者，如果当地获批且可获得，应该用T-DM1代替曲妥珠单抗进行辅助治疗【I级证据A级推荐】。
对于筛选后高风险患者，之前未行双重阻断治疗，可以考虑用奈拉替尼延长抗HER2治疗，并且进行适当的腹泻预防和治疗【I级证据B级推荐，临床获益量表评分：A】。
图3、HER2阳性乳腺癌治疗
Anti-HER2 therapy Recommendations:
(Neo)Adjuvant trastuzumab is highly effective and should be given to all HER2-positive early breast cancer patients who do not have contraindications for its use, with the possible exception of selected cases with very low risk, such as T1aN0 tumours [I, A]
If a HER2 test result is ultimately deemed to be equivocal, even after reflex testing with an alternative assay, HER2-targeted therapy may also be considered [V, B].
One year of (neo)adjuvant trastuzumab remains a standard for the vast majority of HER2-positive patients [I, A].
In highly selected, low-risk patients who receive anthracycline/taxane-based ChT, shortening trastuzumab duration to 6 months may be discussed [I, A].
Trastuzumab should usually not be given concomitantly with anthracycline-based ChT [I, D]; it can be safely combined with non-anthracycline-based ChT (i.e. taxanes) and its concomitant use is more effective than sequential treatment [I, A].
Regular cardiac monitoring is mandatory before starting and during trastuzumab treatment [I, A].
Dual blockade with trastuzumab/lapatinib has not led to improved long-term outcomes and cannot therefore be recommended [I, E].
Dual blockade with trastuzumab/pertuzumab can be considered in high-risk patients, defined as N-positive or ER-negative, for the duration of 1 year, starting before or after surgery [I, A; MCBS v1.1 score: B].
In cases of residual invasive disease after completion of neoadjuvant ChT combined with anti-HER2 therapy, adjuvant trastuzumab should be replaced by adjuvant T-DM1, once approved and where available [I, A].
Extended anti-HER2 therapy with neratinib may be considered in selected high-risk patients, not previously treated with dual blockade, and with appropriate diarrhoea prophylaxis and management [I, B; MCBS v1.1 score: A].
术前初步（新辅助）全身治疗推荐意见：
初步全身治疗应该用于减少局部晚期和肿瘤较大的可手术乳腺癌手术范围，尤其当肿瘤太大需要进行乳房切除术前【I级证据A级推荐】。对于所有肿瘤大于2厘米的患者，如有必要也应该考虑化疗，尤其三阴性乳腺癌和HER2阳性乳腺癌【I级证据B级推荐】。
术前用药和治疗方案应该按照与术后相同的原则进行选择【I级证据A级推荐】。对于绝大多数患者，推荐蒽环类和紫杉类的先后方案【I级证据B级推荐】。
对于三阴性乳腺癌和（或）BRCA基因有害突变患者，可以考虑加入铂类化合物【I级证据C级推荐】。
如果进行初步全身治疗，所有化疗应该术前进行【I级证据B级推荐】。
对于标准新辅助化疗后未达病理学缓解的高风险、三阴性乳腺癌患者，术后可以加6～8轮的卡培他滨【I级证据C级推荐】。
对于需要初步全身治疗而无明确化疗指征的雌激素受体阳性HER2阴性乳腺癌绝经后患者，应该考虑术前内分泌治疗（4～8个月或直至最大缓解）并且术后继续【I级证据A级推荐】。
Primary (neoadjuvant) systemic therapy Recommendations:
PST should be used to reduce the extent of surgery in locally advanced and large operable cancers, in particular when mastectomy is required due to tumour size [I, A]. It should also be considered in all patients with tumours > 2 cm for which ChT is deemed necessary, in particular with triple-negative and HER2-positive subtypes [I, B].
Drugs and drug regimens used in preoperative setting should be selected according to rules identical to those in postoperative setting [I, A]. A sequential regimen of anthracyclines and taxanes is recommended for the vast majority of patients [I, B].
The addition of a platinum compound may be considered in triple-negative tumours and/or in patients with deleterious BRCA1/2 mutations [I, C].
If PST is used, all ChT should be delivered preoperatively [I, B].
In high-risk, triple-negative patients not achieving pCR after standard neoadjuvant ChT, the addition of 6-8 cycles of capecitabine postoperatively may be considered [I, C].
In postmenopausal patients with ER-positive/HER2-negative cancers requiring PST and without a clear indication for ChT, preoperative ET (4-8 months or until maximum response) should be considered and continued postoperatively [I, A].
双膦酸盐用于早期乳腺癌推荐意见：
推荐将双膦酸盐用于低雌激素水平（卵巢功能抑制或绝经后）早期乳腺癌女性，尤其高复发风险患者【I级证据A级推荐】。
推荐将双膦酸盐用于乳腺癌治疗所致骨质疏松患者【I级证据A级推荐】。
Bisphosphonates for early breast cancer Recommendations:
Bisphosphonates for early breast cancer are recommended in women with low-oestrogen status (undergoing OFS or postmenopausal), especially if at high risk of relapse [I, A].
Bisphosphonates are also recommended in patients with treatment-related bone loss [I, A].
老年患者治疗推荐意见：
考虑到体弱患者的温和治疗方案较少，老年早期乳腺癌患者的治疗应该适应其生物学年龄（而非实际年龄）。对于适合标准化疗的患者，应该采用标准多药方案【II级证据B级推荐】。
做出治疗决策之前，应该进行老年评定【II级证据A级推荐】。
Treatment of elderly patients Recommendations:
Treatment of elderly early breast cancer patients should be adapted to biological (not chronological) age, with consideration of less aggressive regimens in frail patients. In patients suitable for standard ChT, a standard multidrug regimen should be used [II, B].
A geriatric assessment should be performed prior to making treatment decisions [II, A].
男性乳腺癌治疗推荐意见：
他莫昔芬是男性乳腺癌患者的内分泌辅助治疗标准方案【IV级证据A级推荐】。
如果对他莫昔芬存在绝对禁忌症，可以考虑芳香酶抑制剂加黄体激素释放激素激动剂，但是必须与患者讨论其较高的毒性，以避免无法坚持用药问题【IV级证据B级推荐】。
芳香酶抑制剂单药不应该用于男性乳腺癌患者的内分泌辅助治疗【IV级证据E级推荐】。
化疗和抗HER2治疗指征和治疗方案应该遵循与女性乳腺癌患者相同的推荐意见【IV级证据A级推荐】。
Treatment of male breast cancer Recommendations:
Tamoxifen is the standard adjuvant ET for male breast cancer patients [IV, A].
If a strong contraindication exists for the use of tamoxifen, a combination of an AI plus a luteinizing hormone-releasing hormone (LHRH) agonist may be considered, but its higher toxicity must be discussed with the patient to avoid compliance issues [IV, B].
An AI alone should not be used as adjuvant ET in male breast cancer patients [IV, E].
ChT and anti-HER2 therapy indications and regimens should follow the same recommendations as those for breast cancer in female patients [IV, A].
乳腺导管原位癌全身辅助治疗推荐意见：
乳腺导管原位癌局部保守治疗后，他莫昔芬和芳香酶抑制剂可以用于预防局部复发并且减少第二原发乳腺癌的发生风险【I级证据B级推荐】。
乳腺导管原位癌乳房切除术后，他莫昔芬或芳香酶抑制剂可以考虑用于减少新发乳腺肿瘤高风险患者的对侧乳腺癌风险【II级证据B级推荐】。
Systemic adjuvant therapy for ductal carcinoma in situ Recommendations:
Both tamoxifen and AIs may be used after conservative local treatment for DCIS to prevent local recurrence and to decrease the risk of development of a second primary breast cancer [I, B].
Following mastectomy for DCIS, tamoxifen or AIs might be considered to decrease the risk of contralateral breast cancer in patients who are at a high risk of new breast tumours [II, B].
个体化治疗推荐意见：
激素受体、孕激素受体和HER2状态应该指导所有全身治疗决策【I级证据A级推荐】。
根据激素受体、孕激素受体、HER2和Ki67表达的替代肿瘤分子学表现型应该用于定义乳腺癌亚组人群【I级证据A级推荐】。
尿激酶型纤溶酶原激活物（uPA）纤溶酶原激活物抑制蛋白1（PAI1）或多基因组（例如70基因Mamma Print、21基因Oncotype DX、50基因Prosigna、8基因Endo predict、乳腺癌指数）表达可以与所有临床病理学因素结合，用于指导疑难患者的全身治疗决策，例如管腔B型、HER2阴性、淋巴结阴性、1～3个淋巴结阳性乳腺癌【I级证据A级推荐】。
PERSONALISED MEDICINE Recommendations:
ER, PgR and HER2 status should guide all systemic treatment decisions [I, A].
Surrogate intrinsic tumour phenotypes, based on expression of ER, PgR, HER2 and Ki67 should be used to define subpopulations of breast cancers [I, A].
Expression of uPA-PAI1 or multigene panels, such as MammaPrint, Oncotype DX, EndoPredict, Prosigna or Breast Cancer Index may be used in conjunction with all clinicopathological factors to guide systemic treatment decisions in patients where these decisions are challenging, such as luminal B-like/HER2-negative and node-negative/nodes 1-3-positive breast cancer [I, A].
Ann Oncol. 2019 Jun 4. [Epub ahead of print]
Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio IT, Zackrisson S, Senkus E; ESMO Guidelines Committee.
Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal; Europa Donna Cyprus, Nicosia, Cyprus; Cancer Institute Hospital, Tokyo, Japan; Centre Jean Perrin, Clermont-Ferrand; Université d'Auvergne, Clermont-Ferrand, France; Institut Curie, Paris; Paris Sciences & Lettres - PSL University, Paris, France; Clinica Universidad de Navarra, Madrid, Spain; Lund University, Malmo, Sweden; Medical University of Gdańsk, Gdańsk, Poland.
KEYWORD: early breast cancer, diagnosis, treatment, follow-up
PMID: 31161190
DOI: 10.1093/annonc/mdz173
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